1. Field of the Invention
The invention relates to a method and apparatus for determining physiological parameters indicative of lung condition, which parameters are independent of air flow rates based on nitrogen monoxide content in exhalation, which content is dependent on air flow rates.
2. Description of the Prior Art
The concentration of nitric oxide (NO) that appears in the exhaled breath depends strongly on several factors including the presence of inflammation. The fact that inflammatory diseases, such as bronchial asthma, elevate exhaled NO has generated great interest in using exhaled NO as a non-invasive index of pulmonary inflammation. Unfortunately, many early reports collected NO levels under different experimental conditions, and the absolute concentrations, as well as the conclusions, were not consistent. Subsequent work demonstrated that the exhaled NO level also depends on many additional factors including the exhalation flow rate, and the position of the soft palate (which affects nasal cavity contribution). These findings generated formal recommendations by both the American Thoracic Society (ATS) and the European Respiratory Society (ERS) on the conditions under which exhaled NO should be collected. Both reports recommend a constant exhalation flow rate during the maneuver (ERS recommends 250 ml/s, the ATS recommends 50 ml/s).
Recently, several groups have demonstrated that exhaled NO arises from both the alveolar and airway regions of the lungs; this conclusion is supported by the presence of nitric oxide synthase (NOS) in cells present in both regions. The flow rate dependence is due to the source of NO in the airways, and this finding prompted the recommendation of a single constant flow rate in all experimental protocols. However, this recommendation presents a critical limitation in the interpretation of the exhaled NO. Namely, the constant flow rate maneuver cannot provide information regarding the origin of the endogenous NO production (i.e. the relative contribution from the airways and the alveoli). As a result, a single exhalation with a constant exhalation flow rate is inherently non-specific, since two subjects can potentially have the same exhaled NO concentration, yet different relative contributions from the airways and alveoli. For example, two subjects with different inflammatory diseases (i.e., asthma and allergic alveolitis) could have identical exhaled NO levels at a constant exhalation flow. The exhaled NO from the patient with asthma would largely arise from the airways, while the exhaled NO from the patient with allergic alveolitis (alveolar inflammation) would largely arise from the alveolar region. However, by using only the exhaled concentration at a single expiratory flow as an index, the diseases could not be distinguished.
To avoid this problem, the prior art has used a technique that utilized multiple single exhalation maneuvers at different constant exhalation flow rates as a means of separately determining airway and alveolar contributions. The airway contribution was characterized by the flux from the airway wall (moles NO/s or ml NO/s) and the alveolar contribution by the steady state alveolar concentration (ppb). Recently, two research groups reported an alternative technique in which the flux from the airway compartment 10 was characterized by two terms—the airway diffusing capacity and either the airway wall concentration or the maximum rate of production of NO by the airways which enters the airstream (maximum flux of NO from the airways). This was achieved by utilizing very low constant expiratory flow rate maneuvers. All of the previous techniques require multiple single exhalations, and the accuracy (or confidence level) of the estimated parameters is positively correlated with the number of single exhalations utilized. Multiple breathing maneuvers are cumbersome and time consuming. Furthermore, constant flow rate maneuvers can be difficult to perform, especially at very low flows and by young subjects.
What is needed is a technique to characterize NO exchange parameters without requiring a constant flow rate.